SR 53 continues north through the mountains and treacherous terrain of the Highland Rim, as at this it becomes narrow and curvy, before crossing into DeKalb County, just after passing through the community of Gassaway.

They pass through farmland, crossing a bridge over the Caney Fork River and having an intersection with SR 264 until the highway reaches Chestnut Mound.

SR 53 then splits off from US 70N/SR 24 and once again becomes a secondary route as it becomes narrow and curvy due to entering mountains again as it crosses into Jackson County.

[3] SR 53 continues north through hilly terrain (as Granville Highway) as a narrow and curvy road as it leaves Chestnut mound and crosses a bridge over an arm of Cordell Hull Lake/Cumberland River to enter Granville, where it passes right through downtown and meets the eastern end of SR 96.

It then leaves Granville and crosses another arm of Cordell Hull Lake/Cumberland River to east and continue through hilly terrain.

[6] After it passes through Celina, SR 53 goes in a northeasterly direction, over the Obey River, skirting the banks of Dale Hollow Lake until it reaches its northern terminus at the Kentucky state line.

Much of SR 53 between Celina and Byrdstown was flooded as a result of the impounding of the Obey River to build the Dale Hollow Dam.

The remnants of the former SR 53 east of Dale Hollow Lake is now signed as Tennessee State Route 325.

53,[12][13] and part of the initial route of Enigma Road was flooded by a shallow bay of Cordell Hull Reservoir.